Our body is home to trillions of microorganisms, most of which live in our gut. Many of these microbes are “good bacteria,” species that stimulate a healthy immune system, or help to outcompete “bad” bacteria that can cause disease. Emerging data indicate that this gut “microbiome” sends signals to the brain, and that they can regulate many aspects of nervous system function, behavior, and even our response to injury. What happens to the balance of good versus bad bacteria following a concussion, in chronic pain, or in the context of neurological diseases? Does the composition of the gut microbiome predispose people to different neurological conditions?

My lab studies the interplay between the immune system, nervous system, and microbiome. Our goal is to better understand how these three systems interact following injury, during the pain response, and in disease states. We already know some of the ways these systems interact. For example, cells of the gut produce serotonin, a chemical that is used by brain cells to communicate; T cells, a type of immune cell, that are stimulated by gut bacteria can infiltrate the central nervous system to affect autoimmune diseases; and bacteria secrete metabolites and toxins that affect brain cells. Our previous work has shown that molecules secreted by the bacterium Staphylococcus aureus bind to and activate pain-sensing sensory neurons, and directly induce pain. We recently found that several distinct types of commensal, or resident, gut microbes directly activate pain-sensing neurons, whereas other types do not.

To better understand how the gut microbiome can cause pain, and whether the profile of the host microbiome is an active factor that modulates the neuroinflammation that underlies pain, my lab takes advantage of germ-free mice, which are raised in sterile conditions and are free from gut microbes. This study is being conducted in collaboration with Dennis Kasper, MD, William Ellery Channing Professor of Medicine at HMS and a fellow faculty member in the Department of Microbiology and Immunology and a world expert on the microbiome. By introducing individual species of bacteria into the germ-free system, we can begin to identify causal links between a particular species of bacteria and their effect on pain sensation. We can then home in on the chemical basis for how this occurs by profiling the molecules released by the bacterium, and even determine the host’s immune response to exposure to the specific bacterial species. Thus, by combining techniques in neuroscience, microbiology, and immunology, we are beginning to define mechanisms by which microbes affect nervous system function.

As new advances are made in this area of research, new and exciting questions arise. For example, does the nervous system differentially respond to good or bad microbes? Does the nervous system also regulate the microbiome in a way that benefits the bacteria? How do existing drug treatments for brain injury, pain, or neurodegenerative disease affect the balance of microbes in the body, and thus the nature of signaling along the gut-brain axis? Does a patient suffering from a concussion or chronic pain have a different microbiome profile? In the coming years, answers to these important questions will enable the development of new therapies for nervous system injury, pain, and disease.

Since its founding in 1990, the Harvard Mahoney Neuroscience Institute has helped advance neuroscience at Harvard Medical School by promoting public awareness of the importance of brain research and by helping to fund research at the School's Department of Neurobiology.

ON THE BRAIN

Since 1992, the Harvard Mahoney Neuroscience Institute has published On The Brain, a newsletter aiming to educate the public on the latest scientific discoveries about the brain.